Effect of Sex Hormones on Crystal Formation in a Stone-forming Rat Model

ObjectivesTo evaluate the contribution of sex hormones in urolithiasis using a stone-forming rat model. Gender differences because of sex hormones are thought to influence the incidence of urolithiasis.MethodsWe divided rats into 7 groups, such as intact males, orchidectomized males, intact males subcutaneously implanted with testosterone, intact males subcutaneously implanted with estradiol, intact females, ovariectomized females, and intact females subcutaneously implanted with testosterone. At 10 weeks old, the rats were fed 0.5% ethylene glycol in drinking water and given 0.5 μg of 1,25-dihydroxy vitamin D3. Kidney crystal deposition and the degree of oxidative stress were examined in each group, and endogenous oxalate metabolism and antioxidant enzymes were compared among groups using real-time reverse transcription-polymerase chain reaction.ResultsExtensive crystal deposition was observed in intact males and testosterone-administered males, whereas few crystals were found in intact females. Crystal deposition was inhibited in orchiectomized males and in those administered estradiol, whereas ovariectomized females and testosterone-administered females had slightly enhanced and very enhanced crystal deposition, respectively. Increases in urinary oxalate excretion paralleled renal crystal deposition, which were both enhanced by testosterone treatment through increased glycolate oxidase expression. Oxidative stress increased in groups with extensive crystal deposition compared with those without. Antioxidant enzyme expression was enhanced by estradiol.ConclusionsTestosterone was a promoter and estradiol an inhibitor of kidney crystal deposition, likely because of their effects on oxalate synthesis and oxidative stress.